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European School of Genetic Medicine Eye Genetics European School of Genetic Medicine th 4 Course in Eye Genetics Bertinoro, Italy, September 27-29, 2015 Bertinoro University Residential Centre Via Frangipane, 6 – Bertinoro www.ceub.it Course Directors: R. Allikmets (Columbia University, New York) A. Ciardella (U.O. Oftalmologia, Policlinico Sant’ Orsola, Bologna) B. P. Leroy (Ghent University, Ghent) M. Seri (U.O Genetica Medica, Bologna). th 4 Course in Eye Genetics Bertinoro, Italy, September 27-29, 2015 CONTENTS PROGRAMME 3 ABSTRACTS OF LECTURES 6 ABSTRACTS OF STUDENTS POSTERS 26 STUDENTS WHO IS WHO 39 FACULTY WHO IS WHO 41 2 4TH COURSE IN EYE GENETICS Bertinoro University Residential Centre Bertinoro, Italy, September 27-29, 2015 Arrival day: Saturday, September 26th September 27 8:30 - 8:40 Welcome 8:40 - 9:10 History of Medical Genetics Giovanni Romeo 9:15 - 10:00 2 parallel talks: (40 min + 5 min discussion) Garrison Room 1. Overview of clinical ophthalmology for basic scientists Antonio Ciardella Jacopo da Bertinoro Room 2. Overview of basic medical genetics for ophthalmologists Bart Leroy 10:05 - 11:35 2 talks (40 min + 5 min discussion) 3. Stargardt disease, the complex simple retinal disorder Rando Allikmets 4. Overview of inherited corneal disorders Graeme Black 11:35 - 12:00 Break 12:00 - 13:30 2 talks (40 min + 5 min discussion) 1. Molecular basis of non-syndromic and syndromic retinal and vitreoretinal diseases Wolfgang Berger 2. Introduction to next-generation sequencing for eye diseases Lonneke Haer-Wigman 13:30 - 14:30 Lunch 14:30 - 16:15 3 parallel workshops Garrison room WS1 Preparation: Student discussion group on interesting cases (clinical, molecular, families, etc.) they have encountered (Black & Leroy) 3 Jacopo da Bertinoro room WS4 Genetic counseling (Hall & Seri) Computer room WS5 Genomics: technological developments and interpretation of results; the impact of next generation sequencing on retinal disease gene identification (Cremers & Haer-Wigman) 16:15 - 16:45 Break 16:45 - 18:30 3 parallel workshops Garrison Room WS1 Preparation: Student discussion group on interesting cases (clinical, molecular, families, etc.) they have encountered (Black & Leroy) Jacopo da Bertinoro room WS2 Clinical approach to hereditary retinal diseases (Ciardella, Graziano, Sodi) Computer room WS3 Disease-causing mutations: finding, interpretation, nomenclature (Berger & Allikmets) September 28 9:00 - 11:15 3 talks (40 min + 5 min discussion) 1. Genetics of RP/LCA/CSNB Bart Leroy 2. Stem cells in eye diseases Jane Sowden 3. Genetics of AMD Rando Allikmets 11:15 - 11:45 Break 11:45 - 13:15 2 talks (40 min + 5 min discussion) 4. AAV vectors for gene retinal therapy Alberto Auricchio 5. Modifier genes and digenic inheritance in retinal diseases Frans Cremers 13:15 - 14:15 Lunch 14:15 - 16:00 3 parallel workshops Jacopo da Bertinoro Room WS2 Clinical approach to hereditary retinal diseases (Ciardella, Graziano, Sodi) Garrison Room WS4 Genetic counseling (Hall & Seri) Computer room 4 WS3 Disease-causing mutations: finding, interpretation, nomenclature (Berger & Allikmets) 16:00 - 16:30 Break 16:30 - 18:15 2 parallel workshops Jacopo da Bertinoro Room WS1 Final preparation for student presentations and selection of 10-12 cases for presentation (Black & Leroy) Computer room WS5 Genomics: technological developments and interpretation of results; the impact of next generation sequencing on retinal disease gene identification (Cremers & Haer-Wigman) September 29 9:00 - 11:15 3 talks (40 min + 5 min discussion) 1. Architecture of genetic disease: causes, modifiers and the concept of genetic load Nicholas Katsanis 2. Genetics of glaucoma Jane Sowden 3. Overview of developmental eye anomalies Graeme Black 11:15 - 11:45 Break 11:45 - 13:15 2 talks (40 min + 5 min discussion) 4. The role for non-coding RNAs in eye development, function and diseases Sandro Banfi 5. Retinal ciliopathies: diverse phenotypes with overlapping genetic structure Nicholas Katsanis 13:15 - 14:15 Lunch 14:15 - 15:45 Student presentations 15:45 - 16:15 Break 16:15 - 17:45 3 shorter talks (25 min +5 min discussion) 6. Genetics of mitochondrial diseases and retinopathies Bart Leroy 7. Mitochondrial optic neuropathies Piero Barboni 8. The paradigm of mitochondrial optic neuropathies: naturally occurring compensatory strategies and treatment options Valerio Carelli 18:00 - 19:00 Feedback on student presentations, awards presentation, summary of the course 5 ABSTRACTS OF LECTURES September, 27th History of Medical Genetics Giovanni Romeo University of Bologna, European School of Genetic Medicine, Bologna, Italy The main steps in the evolution of contemporary Human/Medical Genetics will be summarized and each step will be linked to the professional history of a scientist or clinician who left a mark in our field. Along with the research blooming in this period (see figure), some educational initiatives were developed in America and Europe, like the Short Course in Medical Genetics started by V.A. McKusick in Bar Harbor, Maine-USA, in 1960, the European School of Genetic Medicine started in Sestri Levante, Italy, in 1988 and the Latin American School of Human and Medical Genetics started by Roberto Giugliani in Caxias do Sul, Brazil, in 2005. During the same years these courses and schools trained thousands of young geneticists coming from all over the world and contributed to the transition from genetic to genomic medicine. Evolution of Human/Medical Genetics 1960 1970 1980 1990 2000 2010 Cytogenetics 1956 Biochemical and Somatic Cell Genetics Molecular Genetics and Sequencing From Cloning to “Gene Targeting” Human Genome Project Personalized Medicine Drug & Gene Rx 6 Overview of Clinical Ophthalmology for Basic Scientists Antonio Ciardella Sant’Orsola Malpighi Hospital, Bologna – Italy This overview illustrates the use of clinical tools in the diagnosis of congenital retinal diseases. In particular it covers four hereditary conditions: 1. North Carolina Macular Dystrophy 2. Autosomal Recessive Bestrinopathies 3. Familial Amyloid Polineuropathy with Ocular Involvement 4. Enhanced S-Cone Syndrome In each of the above diseases will be illustrated the clinical characteristics, and the utility of diagnostic techniques such as Fluorescein and Indocyanine Green Angiography (FAG / ICG), Optical Coherence Tomography (OCT), Fundus Autofluorescence (FAF) and Electrophysiology. Overview of Basic Medical Genetics for Ophthalmologists Bart P Leroy, MD, PhD Dept of Ophthalmology & Ctr for Medical Genetics, Ghent University Hospital & Ghent University, Ghent, Belgium & Division of Ophthalmology & Center for Cellular and Molecular Therapeutics The Children's Hospital of Philadelphia, University of Pennsylvania Medical genetics is the young, dynamic and rapidly expanding medical specialty studying variability of phenotypes and genotypes of human disease. Humans are thought to have between 20.000 and 25.000 genes. Of these, 278 genes (238 cloned) are now known to cause inherited retinal & optic nerve disease (RetNet @ http://www.sph.uth.tmc.edu/RetNet/). The presentation will focus on explaining the current insights into genetics to an audience of ophthalmologists. Topics will include a review of mendelian inheritance types and using pedigrees in the ophthalmic genetics clinic, a medical genetics glossary, mitosis and meiosis, current techniques in cytogenetics such as karyotyping, micro-array CGH, molecular mechanisms of disease such as different types of mutations and their respective effects such as point mutations, insertions and deletions, splice site mutations and their effects on protein formation, and methods of gene mapping. Finally a brief review of current techniques of prenatal and pre-implantation genetic diagnosis will be mentioned. Several excellent textbooks on medical genetics exist. Two of particular interest to course participants are: 1/ LB Jorde, JC Carey and MJ Bamshad: Medical Genetics, 4th Edition, Mosby Elsevier, 2010 (ISBN 978-0-323-05373-0) 2/ T Strachan & A Read: Human Molecular Genetics, 4th Edition, Garland Science, 2011 (ISBN 978-0-815-34149-9) A book that needs to be in the library of anyone who interested in genetic eye disease is: 7 Genetic Diseases of the Eye”, 2nd Edition, Edited by EI Traboulsi, Oxford University Press; ISBN- 10: 0195326148; ISBN-13: 978-0195326147; Publication Date: December 29, 2011 A more recent superb textbook which provides concise chapters on most inherited retinal diseases is “Inherited Chorioretinal Dystrophies”, Edited by Bernard Puech, Jean-Jacques De Laey & Graham E Holder, Springer-Verlag, Berlin Heidelberg, 2014, ISBN 978-3-540-69464-9 Stargardt disease, the Complex Simple Retinal Disorder Rando Allikmets Dept. of Ophthalmology, Columbia University, USA The ABCA4 (then called ABCR) gene was cloned in 1997 as the causal gene for autosomal recessive Stargardt disease (STGD1, MIM 248200).1 STGD1 is usually presents as a juvenile-onset macular dystrophy associated with rapid central visual impairment, progressive bilateral atrophy of the foveal retinal pigment epithelium, and the frequent appearance of yellowish flecks, defined as lipofuscin deposits, around the macula and/or in the central and near-peripheral areas of the retina.2 Most STGD1 patients exhibit accumulation of lipofuscin throughout the retina, which is seen as a ‘dark’ choroid on fluorescein angiography3 or, more recently, as an elevated autofluorescence in scanning laser ophthalmoscope (SLO) images.4-6 Subsequently, ABCA4 mutations were found to co-segregate with retinal dystrophies of substantially
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